Method and apparatus for assessing cardiac output in veno-arterial extracorporeal blood oxygenation

ABSTRACT

A system for calculating cardiac output (CO) of a patient undergoing veno-arterial extracorporeal oxygenation includes measuring first oxygenated blood flow rate by a pump in the extracorporeal blood oxygenation circuit as introduced into an arterial portion of the patient circulation system and a corresponding arterial oxygen saturation, then changing the pump flow rate, such as decreasing, to produce a corresponding change in arterial oxygen saturation (wherein such change is outside of normal operating variances, operating errors or drift), which change in the arterial oxygen saturation is measured. From the first flow rate and the second flow rate along with the corresponding measured arterial oxygen saturation, the CO of the patient can be calculated, without reliance upon a measure of venous oxygen saturation. Alternatively, the CO of the patient can be calculated, without reliance upon a change in flow rate by changing a gas exchange with the blood in the extracorporeal blood oxygenation circuit to impart corresponding changes in a blood parameter in the arterial portion of the patient circulation system and the blood delivered from the extracorporeal blood oxygenation circuit.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. Provisional Pat.Application 62/798,269 filed Jan. 29, 2019 entitled METHOD AND APPARATUSFOR ASSESSING CARDIAC OUTPUT IN VENO-ARTERIAL EXTRACORPOREAL BLOODOXYGENATION and which is hereby expressly incorporated by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT

Not applicable.

REFERENCE TO A SEQUENCE LISTING

Not applicable.

STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINTINVENTOR

Not applicable.

BACKGROUND OF THE INVENTION

The present disclosure relates to assessing cardiac output of a patientoperably connected to a veno-arterial (VA) extracorporeal circuit, andparticularly a veno-arterial extracorporeal blood oxygenation circuitsuch as, but not limited to, a veno-arterial extracorporeal membraneoxygenation (ECMO) circuit.

VA ECMO is a medical procedure employed in patients who have a heartfailure and in some cases also experiencing life-threatening respiratoryfailure, typically Acute Respiratory Distress Syndrome (ARDS). Patientsmay also need VA ECMO after heart surgery if the heart does not recover.The combination of lung and heart failure is often observed inprematurely born neonates.

The lack of oxygen delivery due to low cardiac output (CO) andcompromised lung performance causes damage to the tissue and canultimately lead to the death of the patient. Extracorporeal bloodoxygenation, such as VA ECMO, supplements or replaces blood oxygenationby the lungs and supplants the heart of the patient.

In VA ECMO, a large venous (access) cannula is inserted usually throughthe jugular (or the femoral) vein with the cannula tip located near theright atrium to withdraw blood. These cannulae are then connected to anextracorporeal circuit which includes a pump and a membrane oxygenator.In children and in some adults, blood is usually delivered back to thepatient in the ascending aorta. Also, adults often have the bloodwithdrawn via a femoral venous (access) catheter with a tip close to theright atria and delivered via a femoral arterial (return) catheter witha tip in the descending aorta.

There are multiple variations of connection, however, in each thepatient blood is continuously circulated through the extracorporealcircuit by being withdrawn from the patient, then circulated through anoxygenator, such as a membrane oxygenator, where the blood isoxygenated. Then the blood is returned to the patient where the nowoxygenated blood is pumped into the aorta where it mixes with bloodcoming from the heart.

While cardiopulmonary support offers life-saving and life prolongingtreatment, the intrusive nature of the cardiopulmonary VA ECMO supportcarries significant risks and potential complications. Each additionalhour of unnecessary VA ECMO cardiopulmonary support increases theprobability of negative complications like bleeding and clotting as wellas increasing the already substantial costs of the treatment. Therefore,it is desirable to limit the duration of cardiopulmonary support asrequired by the individual patient. One of the main criteria fordecreasing or terminating cardiopulmonary support is an adequateincrease in the ability of the heart to pump blood, that is the cardiacoutput increases. Thus, the earlier that a physician can identify therecovery of the heart, the faster the patient can be removed from VAECMO, if the lungs have also recovered. Alternatively, if the heart hasrecovered but the lungs have not recovered or remain problematic, suchas not providing sufficient oxygenation, the patient can be moved to WECMO, which is a more stable procedure and the patient can be on W ECMOfor a longer duration, especially for patients having a sufficientlyworking heart.

Current standard methods to measure cardiac output (CO) include (i)pulmonary artery thermodilution which is invasive and cannot be used insmall children, and (ii) transpulmonary thermodilution which is alsoinvasive and typically has less accuracy in the VA ECMO setting.

Therefore, the need exists for improved systems and methods of measuringcardiac output (CO) during veno-arterial extracorporeal bloodoxygenation.

BRIEF SUMMARY OF THE INVENTION

Generally, the present disclosure provides a non-invasive methods andapparatus to measure cardiac output (CO), in a patient operablyconnected to a veno-arterial extracorporeal circuit, and particularly aveno-arterial extracorporeal blood oxygenation circuit such as but notlimited to a veno-arterial extracorporeal membrane oxygenation (VA ECMO)circuit.

In one configuration, a first flow rate from a pump in an extracorporealcircuit and an arterial oxygen saturation are measured, then the pumpflow rate is changed, such as decreased (or increased), to produce acorresponding change in arterial oxygen saturation (such change beingoutside of normal operating variances, operating error or drift), andthe second flow rate from the pump and the new arterial oxygensaturation are recorded. From the first pump flow rate, the second pumpflow rate and the corresponding first and second arterial oxygensaturation corresponding to the first pump flow rate and the second pumpflow rate, the CO of the patient can be calculated.

In another configuration, a method is provided for calculating cardiacoutput of a patient undergoing veno-arterial extracorporeal oxygenation,wherein the method includes withdrawing blood from a first venousportion of a patient circulation system to pass the withdrawn blood intoa veno-arterial extracorporeal blood oxygenation circuit, theveno-arterial extracorporeal circuit having an access line, a returnline and a blood oxygenator intermediate the access line and the returnline, such that the withdrawn blood enters the extracorporeal bloodoxygenation circuit through the access line; pumping the withdrawn bloodthrough the access line and the blood oxygenator to form oxygenatedblood; pumping the oxygenated blood from the oxygenator and through thereturn line; introducing the oxygenated blood from the return line to anarterial portion of the patient circulation system; measuring a firstblood flow rate through the extracorporeal blood oxygenation circuit(one of the access line, the blood oxygenator and the return line);measuring an arterial oxygen saturation of the patient during the firstblood flow rate; measuring a venous oxygen saturation (or surrogateparameter) of the patient during the first blood flow rate; andcalculating a cardiac output of the patient corresponding to themeasured blood flow rate, the measured arterial oxygen saturation andthe measured venous oxygen saturation.

In a further configuration, the present disclosure provides a method forassessing cardiac output of a patient undergoing veno-arterialextracorporeal blood oxygenation, wherein the method includesestablishing a first blood flow rate from an extracorporeal bloodoxygenation circuit into an arterial portion of a patient circulationsystem; measuring the first blood flow rate; measuring a first arterialoxygen saturation of the patient corresponding to the first blood flowrate; establishing a second blood flow rate from the extracorporealblood oxygenation circuit into the arterial portion of the patientcirculation system; measuring the second blood flow rate; measuring asecond arterial oxygen saturation of the patient corresponding thesecond blood flow rate; and calculating a cardiac output of the patientcorresponding to the first blood flow rate, the second blood flow rate,the first arterial oxygen saturation and the second arterial oxygensaturation.

A further method is disclosed for calculating cardiac output of apatient undergoing veno-arterial extracorporeal oxygenation, the methodincluding withdrawing blood from a venous portion of a patientcirculation system to pass the withdrawn blood into a veno-arterialextracorporeal blood oxygenation circuit, the veno-arterialextracorporeal blood oxygenation circuit having an access line, a returnline and a blood oxygenator intermediate the access line and the returnline, such that the withdrawn blood enters the veno-arterialextracorporeal blood oxygenation circuit through the access line andreturns to the patient circulation system through the return line;passing the withdrawn blood through the access line and the bloodoxygenator to form oxygenated blood; passing the oxygenated blood fromthe oxygenator and through the return line; introducing the oxygenatedblood from the return line to an arterial portion of the patientcirculation system; measuring a first blood flow rate through theextracorporeal blood oxygenation circuit; measuring an arterial oxygensaturation of the patient; measuring a venous oxygen saturation of thepatient; and calculating a cardiac output of the patient correspondingto the measured blood flow rate, the measured arterial oxygen saturationand the measured venous oxygen saturation.

The present disclosure further provides an apparatus for calculatingcardiac output of a patient operably connected to a veno-arterialextracorporeal blood oxygenation circuit, the extracorporeal bloodoxygenation circuit having an access line withdrawing blood from acirculation system of the patient, a blood oxygenator, a pump and areturn line returning oxygenated blood to an arterial portion of thecirculation system, wherein the apparatus includes a controllerconfigured to connect to one of the blood oxygenator and the pump, thecontroller configured to calculate a cardiac output of the patient basedon a measured first flow rate of oxygenated blood from theextracorporeal blood oxygenation circuit, a first arterial oxygensaturation of the patient during the first flow rate, a measured secondflow rate of oxygenated blood from the extracorporeal blood oxygenationcircuit and a second arterial oxygen saturation of the patient duringthe second flow rate.

Also provided is a method for assessing cardiac output of a patientundergoing veno-arterial extracorporeal blood oxygenation, wherein themethod includes measuring a blood flow rate of oxygenated blooddelivered to an arterial portion of a patient circulation system by anextracorporeal blood oxygenation circuit; measuring an arterial oxygensaturation of the patient during the first flow rate; measuring a venousoxygen saturation of the patient during the first flow rate; andcalculating a cardiac output of the patient corresponding to themeasured blood flow rate, the measured arterial oxygen saturation andthe measured venous oxygen saturation.

A further method is provide for assessing cardiac output of a patientundergoing veno-arterial extracorporeal blood oxygenation, wherein themethod includes establishing a first blood flow rate from anextracorporeal blood oxygenation circuit into an arterial portion of apatient circulation system; measuring the first blood flow rate;measuring a first value of a blood parameter in an arterial portion ofthe patient circulation system corresponding to the first blood flowrate; establishing a second blood flow rate from the extracorporealblood oxygenation circuit into the arterial portion of the patientcirculation system; measuring the second blood flow rate; measuring asecond value of the blood parameter in the arterial portion of thepatient circulation system corresponding to the second blood flow rate;and calculating a cardiac output of the patient corresponding to thefirst blood flow rate, the second blood flow rate, the first value ofthe blood parameter, and the second value of the blood parameter. It isundertood the method can further include measuring the first value ofthe blood parameter during the first blood flow rate from theextracorporeal blood oxygenation circuit; or wherein measuring the firstvalue of the blood parameter corresponding to the first blood flow rateincludes measuring the first value of the blood parameter in an arterialportion of the patient circulation system; or wherein measuring thefirst value of the blood parameter corresponding to the first blood flowrate includes measuring a first arterial oxygen saturation or whereinmeasuring the first value of the blood parameter corresponding to thefirst blood flow rate includes measuring a first arterial oxygensaturation in an arterial portion of the patient circulation system.

An apparatus is provided for quantifying a cardiac output of a patientoperably connected to an extracorporeal blood oxygenation circuit, theextracorporeal blood oxygenation circuit having an access linewithdrawing blood from a circulation system of the patient, a bloodoxygenator, a pump and a return line returning oxygenated blood to anarterial portion of the circulation system, the apparatus including acontroller configured to connect to one of the blood oxygenator and thepump, the controller configured to calculate a cardiac output of thepatient based on a measured first flow rate of oxygenated blood from theextracorporeal circuit into the patient circulation system, a firstarterial oxygen saturation of the patient during the first flow rate, ameasured second flow rate of oxygenated blood from the extracorporealcircuit into the patient circulation system and a second arterial oxygensaturation of the patient during the second flow rate.

A further apparatus is provided for quantifying a cardiac output of apatient operably connected to an extracorporeal blood oxygenationcircuit, the extracorporeal blood oxygenation circuit having an accessline withdrawing blood from a circulation system of the patient, a bloodoxygenator, a pump and a return line returning oxygenated blood to anarterial portion of the patient circulation system, the apparatusincluding a controller, the controller connected to one of the bloodoxygenator and the pump, the controller further connected to an oximeterand configured to calculate a cardiac output of the patientcorresponding to a measured blood flow rate in the extracorporeal bloodoxygenation circuit, a measured arterial oxygen saturation by theoximeter and a measured venous oxygen saturation.

An alternative method is disclosed for calculating cardiac output of apatient undergoing veno-arterial extracorporeal blood oxygenation, themethod including establishing a first blood flow rate from anextracorporeal blood oxygenation circuit into an arterial portion of apatient circulation system; measuring the first blood flow rate;establishing a first removal rate of carbon dioxide from the blood in anoxygenator in the extracorporeal circuit; determining (i) at least oneof a first arterial carbon dioxide content or a first arterial carbondioxide content surrogate and (ii) at least one of a first carbondioxide content or a first carbon dioxide content surrogate in the blooddelivered to the patient after passing the oxygenator corresponding tothe first removal rate of carbon dioxide from the blood; establishing asecond removal rate of carbon dioxide from the blood in the oxygenatorin the extracorporeal circuit; determining (i) at least one of a secondarterial carbon dioxide content or a second arterial carbon dioxidecontent surrogate and (ii) at least one of a second carbon dioxidecontent or a second carbon dioxide content surrogate in the blooddelivered to the patient after passing the oxygenator corresponding tothe second removal rate of carbon dioxide from the blood; andcalculating a cardiac output of the patient corresponding to the firstblood flow rate, the at least one of first arterial carbon dioxidecontent or the first arterial carbon dioxide content surrogate, the atleast one of first carbon dioxide content or the first carbon dioxidecontent surrogate; the at least one of second arterial carbon dioxidecontent or the second arterial carbon dioxide content surrogate and theat least one of the second carbon dioxide content or the second carbondioxide content surrogate.

A further alternative method is provided for calculating cardiac outputof a patient undergoing veno-arterial extracorporeal blood oxygenation,the method including establishing a first blood flow rate in anextracorporeal blood oxygenation circuit from a venous portion of apatient circulation system into an arterial portion of the patientcirculation system; measuring the first blood flow rate; establishing afirst exchange rate of a gas with the blood in the extracorporeal bloodoxygenation circuit; measuring a first value of a blood parameter in thearterial portion of the patient circulation system corresponding to thefirst exchange rate; measuring a first value of the blood parameter inthe blood delivered to the patient corresponding to the first exchangerate; establishing a second exchange rate of the gas with the blood inthe extracorporeal blood oxygenation circuit; measuring a second valueof the blood parameter in the arterial portion of the patientcirculation system corresponding to the second exchange rate; measuringa second value of the blood parameter in the blood delivered to thepatient corresponding to the second exchange rate; and calculating acardiac output of the patient corresponding to the first blood flow rateand (x) the first value of a blood parameter in an arterial portion ofthe patient circulation system corresponding to the first exchange rate,(xx) the first value of the blood parameter in the blood delivered tothe patient corresponding to the first exchange rate, (y) the secondvalue of the blood parameter in the arterial portion of the patientcirculation system corresponding to the second exchange rate and (yy)the second value of the blood parameter in the blood delivered to thepatient corresponding to the second exchange rate.

An alternative apparatus for quantifying a cardiac output of a patientoperably connected to an extracorporeal blood oxygenation circuit, theextracorporeal blood oxygenation circuit having an access linewithdrawing blood from the circulation system of the patient, a bloodoxygenator, a pump and a return line returning oxygenated blood to anarterial portion of the circulation system, wherein the apparatusincludes a controller configured to connect to one of the bloodoxygenator or the pump, the controller configured to calculate a cardiacoutput of the patient based on a measured first flow rate of oxygenatedblood from the extracorporeal circuit, a first arterial carbon dioxidecontent or surrogate and a first carbon dioxide content or surrogatemeasured during a first flow rate of sweep gas though an oxygenator inthe extracorporeal circuit; and a second arterial carbon dioxide contentor surrogate and a second carbon dioxide content or surrogate measuredduring a second flow rate of sweep gas though the oxygenator in theextracorporeal circuit.

The following will describe embodiments of the present disclosure, butit should be appreciated that the present disclosure is not limited tothe described embodiments and various modifications of the invention arepossible without departing from the basic principles. The scope of thepresent disclosure is therefore to be determined solely by the appendedclaims.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

FIG. 1 is a representative veno-arterial extracorporeal bloodoxygenation circuit.

FIG. 2 is representation of a location of blood introduction and bloodwithdrawal in the veno-arterial extracorporeal blood oxygenationcircuit.

FIG. 3 is representation of an alternative location of bloodintroduction and blood withdrawal in the veno-arterial extracorporealblood oxygenation circuit.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIG. 1 , an extracorporeal blood oxygenation circuit 100 isshown connected to a circulation system 20 of a patient.

The circulation system 20 is a human (or animal) circulatory systemincluding blood, a vascular system, and a heart. For purposes of thisdescription, the circulation system 20 is includes a cardiopulmonarysystem 30 and a systemic system connecting the cardiopulmonary system 30to the tissues of the body. Specifically, the systemic system passes theblood though the vascular system (arteries, veins, and capillaries)throughout the body.

The cardiopulmonary system 30 includes the right heart, the lungs andthe left heart, as well as the vascular structure connecting the rightheart to the lungs, the lungs to the left heart and some portion of theaorta and large veins located between the extracorporeal circuit and theright and left heart. That is, in theory the cardiopulmonary system 30would include only the right heart, the lungs, the left heart and thevascular structure directly connecting the right heart to the lungs andthe lungs to the left heart. However, in practice it is sometimesimpracticable to operably connect the extracorporeal circuit 100immediately adjacent the large vein at the right heart, or immediatelyadjacent the aorta at the left heart. Therefore, the cardiopulmonarysystem 30 often includes a limited length of the veins entering theright heart and the aorta exiting the left heart. For example, theextracorporeal circuit 100 can be connected to a femoral artery andfemoral vein, thereby effectively extending the cardiopulmonary system30 to such femoral artery or vein.

For cardiopulmonary and vascular systems, the term “upstream” of a givenposition refers to a direction against the flow of blood, and the term“downstream” of a given position is the direction of blood flow awayfrom the given position. The “arterial” side or portion is that part inwhich oxygenated blood flows from the heart to the capillaries. The“venous” side or portion is that part in which blood flows from thecapillaries to the heart and lungs (the cardiopulmonary system 30).

The basic components of the extracorporeal circuit (or extracorporealblood oxygenation circuit) 100 for a conventional extracorporealoxygenation machine include an access (or venous) line 110, anoxygenator 120 and heat exchanger (not shown), a pump 130, a return (orarterial) line 140, a sensor 116 in the venous line, a sensor 146 in thearterial line and a controller 160. For purposes of description, theaccess (or venous) line 110 is referred to as the access line and thereturn (or arterial) line 140 is referred to as the return line.

The extracorporeal circuit 100 is configured to form a veno-arterial(VA) extracorporeal circuit 100. In the veno-arterial extracorporealcircuit 100, the site of the withdrawal of blood from the circulationsystem 20 to the extracorporeal circuit 100 is a venous portion of thecirculation system and the site of introduction of blood from theextracorporeal circuit to the circulation system is an arterial portionof the circulation system as shown in FIGS. 2 and 3 .

As seen in FIGS. 2 and 3 , the site of withdrawal of blood from thecirculation system 20 to the extracorporeal circuit 100 can include theinferior vena cava, the superior vena cava and/or the right atria andthe site of introduction of blood from the extracorporeal circuit to thecirculation system can include the aorta, a femoral artery orintermediate arterial vessels.

Thus, the VA extracorporeal circuit 100 withdraws blood from the venousportion of the circulation system 20 (including the cardiopulmonarysystem 30), and returns the blood to the arterial portion of thecirculation system (including the cardiopulmonary system). The withdrawnblood can be treated while it is withdrawn, such as through gas exchangeor oxygenation (ECMO) before being returned to the arterial portion ofthe circulation system 20. The blood treatment can be any of a varietyof treatments including, but not limited to, oxygenation (and carbondioxide withdrawal) or merely circulation (pumping), thereby relievingthe load on the heart.

The access line 110 extends from the venous portion of the circulationsystem 20, and preferably from a venous portion of the cardiopulmonarysystem 30. Referring to FIGS. 2 and 3 , the access line 110 typicallyincludes a venous (or access) cannula 112 providing the fluid connectionto the circulation system 20.

Depending upon the configuration of the extracorporeal circuit 110 andthe mechanisms for measuring the blood parameters, the access line 110can also include or provide an indicator introduction port 114 as thesite for introducing an indicator into the extracorporeal circuit 100.In one configuration, the indicator introduction port 114 forintroducing the dilution indicator is upstream to an inlet of theoxygenator 120. In selected configurations, the introduction site 114can be integrated into the oxygenator 120.

In the access line 110, the sensor 116, if employed, can be a dilutionsensor for sensing passage of the indicator through the extracorporealcircuit 100. The dilution sensor 116 (as well as sensor 146) can be anyof a variety of sensors, and can cooperate with the particularindicator. The sensor 116 (as well as sensor 146) can measure differentblood properties: such as but not limited to temperature, Dopplerfrequency, electrical impedance, optical properties, density, ultrasoundvelocity, concentration of glucose, oxygen saturation and other bloodsubstances (any physical, electrical or chemical blood properties). Itis also understood the sensor 116 can also measure the blood flow rate.Alternatively, there can be a sensor (not shown) in addition to sensor116 be to measure the blood flow rate. Thus, in one configuration thepresent system includes a single blood property sensor and a single flowrate sensor. It is further contemplated that a single combined sensorfor measuring flow rate and a blood parameter (property) can be used. Asset forth herein, in some pumps 130, a rotational speed, RPM (rotationsper minute) of the pump can be measured for providing a measurement ofblood flow rate.

The return line 140 connects the extracorporeal circuit 100 to anarterial portion of the circulation system 20 and in one configurationto an arterial portion of the cardiopulmonary system 30, such as theaorta. Alternatively, the return line 140 can connect to the femoralartery. The return line 140 typically includes a return (arterial)cannula 142 providing the fluid connection to the arterial portion ofthe circulation system 20.

The return line 140 can also include a sensor such as the sensor 146.The sensor 146 can be any of a variety of sensors, as set forth in thedescription of the sensor 116, and is typically selected to cooperatewith the anticipated indicator. While the system is described with thetwo sensors 116, 146, for an enhanced accuracy of indicator dilutionmeasurements, it is understood only a single sensor is necessary.

However, it is understood the sensors 116, 146 can be located outside ofthe extracorporeal circuit 100. That is, the sensors 116, 146 can beremotely located and measure in the extracorporeal circuit 100, thechanges produced in the blood from the indicator introduction or valuesrelated to the indicator introduction which can be transmitted ortransferred by means of diffusion, electro-magnetic or thermal fields orby other means to the location of the sensor.

The oxygenator 120 can be broadly classified into bubble typeoxygenators and membrane type oxygenators. The membrane type oxygenatorsfall under the laminate type, the coil type, and the hollow fiber type.Membrane type oxygenators offer advantages over the bubble typeoxygenators as the membrane type oxygenators typically cause less blooddamage, such as hemolysis, protein denaturation, and blood coagulationas compared with the bubble type oxygenators. Although the preferredconfiguration is set forth in terms of a membrane type oxygenator, it isunderstood any type of oxygenator can be employed.

The pump 130 can be any of a variety of pumps types, including but notlimited to a peristaltic or roller (or impeller or centrifugal) pump.The pump 130 induces a blood flow rate through the extracorporealcircuit 100. Depending on the specific configuration, the pump 130 canbe directly controlled at the pump or can be controlled through thecontroller 160 to establish a given blood flow rate in theextracorporeal circuit. The pump 130 can be at any of a variety oflocations in the extracorporeal circuit 100, and is not limited to theposition shown in the Figures. In one configuration, the pump 130 is acommercially available pump and can be set or adjusted to provide any ofa variety of flow rates wherein the flow rate can be read by a userand/or transmitted to and read by the controller 160.

The controller 160 is typically connectable to the oxygenator 120, thepump 130 and the sensor(s) 116, 146 if employed. The controller 160 canbe a stand-alone device such as a personal computer, a dedicated deviceor embedded in one of the components, such as the pump 130 or theoxygenator 120. Although the controller 160 is shown as connected to thesensors 116 and 146, the pump 130 and the oxygenator 120, it isunderstood the controller can be connected to only the sensors, thesensors and the pump, or any combination of the sensors, pump andoxygenator. In one configuration, at least one of the pump 130 and thecontroller 160 provides for control of the pump and the flow rate of theblood through the pump, respectively. It is also understood, thecontroller 160 also can be connected to an oximeter 60, such as a pulseoximeter, to automatically collect data or oximetry data can be putmanually into controller. Alternatively, the oximeter 60 and thecontroller 160 can be integrated as a single unit.

The controller 160 is programmed with the equations as set forth hereinand can perform the associated calculations based on inputs from theuser or connected components.

The normal or forward blood flow through the extracorporeal circuit 100includes withdrawing blood through the access line 110 from the venousside circulation system 20 (and particularly the venous portion of thecardiopulmonary circuit 30), passing the withdrawn blood through theextracorporeal circuit (to treat such as oxygenate), and introducing thewithdrawn (or treated or oxygenated or circulated) blood through thereturn line 140 into the arterial side of the circulation system. Thepump 130 thereby induces a blood flow at a known (measured) blood flowrate through the extracorporeal circuit 100 from the access line 110 tothe return line 140.

For purposes of the present description, the following terminology isused. Cardiac output CO is the amount of blood pumped out by the leftventricle in a given period of time (typically a 1 minute interval). Theheart capacity (flow) is typically measured by cardiac output CO. Theterm blood flow rate means a rate of blood passage, volume per unittime. The blood flow rate is a volumetric flow rate (“flow rate”). Thevolumetric flow rate is a measure of a volume of liquid passing across-sectional area of a conduit per unit time, and may be expressed inunits such as milliliters per min (ml/min) or liters per minute (l/min).

The current disclosure provides a simple noninvasive technology tomeasure CO in VA extracorporeal blood oxygenation, such as a VA ECMOsetting. To apply the present technique to measure cardiac output COduring VA extracorporeal blood circulation, including oxygenation, suchas ECMO, the following terms are employed:

-   SvOz - mixed venous saturation of blood that did not pass through    the oxygenator 120-   SaO₂ - arterial saturation, (which as set forth below can be    measured by blood sample or by oximetry, including pulse oximetry)-   Q_(b) - extracorporeal flow rate, (which as set forth below can be    measured by a flow rate of the pump 130 in the extracorporeal    circuit 100)-   CO - Cardiac output

Balance Equation

In the first instance, a mass balance equation is applied to theextracorporeal circuit 100. For this analysis, the following assumptionsare made:

-   1. Oxygenation of the blood passing through the lungs is small    (negligible).-   2. Oxygen saturation of the blood after oxygenator is at or near    100%. (The formula below can be adjusted for a different value of    oxygen saturation from the oxygenator.)

With the appropriate accounting for oxygen, an initial equation becomes:

Q_(b) * 100 + CO *SvO₂ = (CO + Q_(b)) * SaO₂

Solving for CO:

Q_(b) * 100 + CO*SvO₂ − Q_(b) * SaO₂ = CO * SaO₂

CO × (SaO₂ − SvO₂) = Qb × (100 − SaO₂)

$CO = Q_{b} \times \frac{\left( {100 - SaO_{2}} \right)}{\left( {SaO_{2} - SvO_{2}} \right)}$

Currently, during VA ECMO treatment, Q_(b) and SaO₂ are routinelymeasured, while SvOz is difficult to measure. That is, the value ofvenous saturation measured pre-oxygenator in extracorporeal (ECMO)circuit 100 may be different from mixed venous saturation in thecardiopulmonary system 30.

Theoretically in equation 4, SvOz should be equal to saturation of bloodcoming from the lungs, thus providing a potential surrogate. If lungsare not working, this assumption that SvOz is close saturation in thelungs is accurate. However, in the case that the lungs are partlyworking, then substituting saturation after the lungs by SvOz willincrease errors in the calculation of CO.

Therefore, Equation 4 can be used with the measured and reliable valuesof Q_(b) and SaO₂ in conjunction with a measured SvO₂, such as measuredin the access line 110, recognizing the measured surrogate value of SvOzvalue may introduce an unacceptable error.

Thus, depending on the confidence in the SvOz value, there are 2unknowns in Equation 4, so the equation can still be used for COcalculation (assessment), but is less accurate.

Two Balance Equations

To increase the accuracy of the CO measurement by eliminating thepotentially unreliable or unknown value of SvO₂, the value of Q_(b)(such as via flow rate of the pump 130 in the extracorporeal circuit100) can be changed, such as by an increase or decrease to deliver adifferent flow rate of 100% oxygenated blood through the return line 140and into the arterial portion of the circulation system 20, such as theaorta. In one configuration, the amount of change in the pump flow rateand the corresponding change in the measured parameters is outside ofnormal operating variances, operating error or drift.

For purposes of description, it is assumed the flow rate of oxygenatedblood from the oxygenator 120 is decreased, such as by decreasing pumpflow rate (where Q_(b(2)) < Q_(b(1))). Thus, less 100% oxygenated bloodis delivered from the extracorporeal circuit 100 and measured on thearterial side of the patient, SaO₂₍₂₎ < SaO₂₍₁₎. From this difference, achange in SaO₂, ΔSaO₂, can be written as:

ΔSaO₂ = SaO₂₍₁₎ - SaO₂₍₂₎

where index “(1)” and “(2)” correspond to a first flow rate delivered bythe extracorporeal circuit 100, such as a first pump setting, Q_(b(1))and a second flow rate delivered by the extracorporeal circuit, such asa second pump setting pump setting Q_(b(2)), respectively.

For this application of two balance equations analogous to Eq. 4, it isassumed the value of CO between the two flow rates through theextracorporeal circuit 100 does not change or that any actual change isinsubstantial or negligible. Thus, the two equations for the twodifferent flow rates of oxygenated blood from the extracorporeal circuit100 are:

$CO = Q_{b{(1)}} \times \frac{\left( {100 - SaO_{2{(1)}}} \right)}{\left( {SaO_{2{(1)}} - SvO_{2{(1)}}} \right)}$

$CO = Q_{b{(2)}} \times \frac{\left( {100 - SaO_{2{(2)}}} \right)}{\left( {SaO_{2{(2)}} - SvO_{2{(2)}}} \right)}$

During the decrease in SaO₂ from SaO₂₍₁₎ to SaO₂₍₂₎, a decrease of SvOzis also expected. However, the magnitude of this decrease in SvOz isunknown. If the magnitude of the decrease in SaO₂ is small, then theassumption is made that SvO₂₍₁₎ ≈ SvO₂₍₂₎, then the system of equations(Eq. 6 and Eq. 7) with 2 unknowns (CO and SvO₂) can be solved for CO,which in turn can then be calculated from the known or measuredQ_(b(1)), Q_(b(2)), and SaO₂₍₁₎ and SaO₂₍₂₎, without relying upon avalue of SvO₂.

However, it is also understood that a decrease of pump flow rateQ_(b(1)) to Q_(b(2)) may lead to the situation that more blood will beavailable (more preload) to the heart and the cardiac output (CO) mayactually increase, and can increase up to the amount of the pump flowrate decrease. So for a cardiac output for the first pump flow rateCO₍₁₎ and the increased cardiac output CO₍₂₎ during the decreased pumpflow rate, the following applies.

CO₍₂₎ − CO₍₁₎ = Q_(b(1))- Q_(b(2))

Thus Equations 6 and 7 become:

$CO_{(1)} = Q_{b{(1)}} \times \frac{\left( {100 - SaO_{2{(1)}}} \right)}{\left( {SaO_{2{(1)}} - SvO_{2{(1)}}} \right)}$

$CO_{(2)} = Q_{b{(2)}} \times \frac{\left( {100 - SaO_{2{(2)}}} \right)}{\left( {SaO_{2{(2)}} - SvO_{2{(2)}}} \right)}$

and consider Eq.8

$CO_{(1)} = Q_{b{(1)}} \times \frac{\left( {100 - SaO_{2{(1)}}} \right)}{\left( {SaO_{2{(1)}} - SvO_{2{(1)}}} \right)}\mspace{6mu}$

$CO_{(1)} + \left( {Q_{b{(1)}} - Q_{b{(2)}}} \right) = Q_{b{(2)}} \times \frac{\left( {100 - SaO_{2{(2)}}} \right)}{\left( {SaO_{2{(2)}} - SvO_{2{(2)}}} \right)}$

In the event that SvO₂₍₁₎ ≈ SvO_(2(2),) then Equations 6B and 7B havingtwo unknowns, CO₍₁₎ and SvO₂₍₁₎ (which equals or approximates SvO₂₍₂₎)can be solved. These can be used for the value of CO can be equal orbetween CO₍₂₎ and CO₍₁₎.

If the decrease of SvO₂₍₁₎ is a portion or fraction of the decrease ofthe arterial saturation, ΔSaO₂, (Eq. 5), then the value SvO₂₍₂₎ =SvO₂₍₁₎ - K^(∗)ΔSaO₂: where K is for example 0.5 (but could be 0.1, 0.2or 0.7 (or whatever the appropriate factor), can be used in Equations 7Aand 7B where the value SvO₂₍₂₎ will be substituted and again, a systemof two equations with two unknowns (CO and SvO₂) or (CO₍₁₎ and SvO₂) isprovided, wherein the equations can be solved to determine CO (CO₍₁₎),without requiring a value or measurement of SvO₂.

Analogously, if the increase of CO₍₁₎ is a portion or fraction of thedecrease of the pump flow, Q_(b(1))-Q_(b(2)), (Eq. 8), then the valueCO(₂) = CO₍₁₎ + R^(∗)(Q_(b(1))-Q_(b(2))): where R is for example 0.5(but could be 0.1, 0.2 or 0.7 (or whatever the appropriate factor), canbe used in Equations 7A and 7B where the value CO₍₂₎ will be substitutedand again, a system of two equations with two unknowns (CO and SvO₂) or(CO₍₁₎ and SvO₂₍₁₎) is provided, wherein the equations can be solved todetermine CO (CO₍₁₎).

Theoretically, it is believed the actual CO will be between the valuecalculated from Equations 6 and 7 and the value calculated fromEquations 6B and 7B. Practically, it is observed that after the decreaseof arterial oxygen saturation, the venous oxygen saturation alsodecreases.

It is believed in case of the lungs partly working (thereby partlyoxygenating the blood) the actual mass balance equations need to includean after-lung situation instead of venous situations. The benefit of thecurrent two flow rate concept is that it is independent of (eliminates)the need for assumptions of venous oxygen saturations in Eq. 4 as usedfor a surrogate of mix venous oxygen saturation. In addition, there maybe intermediate conditions (assumptions) applied to Equations 6 and 7and Equations 6A and 7A, like the assumption that SvO₂₍₂₎ does notdecrease the entire amount of decrease in SaO₂ as per ΔSaO₂, but on aportion such as ⅓ or ⅕ etc., then all the solutions for the CO valuewill be in-between calculation from Equations 6 and 7 and thecalculation from Equations 6A and 7A.

Although Equations 6 and 7 as well as 6A and 7A, and 6b and 7B are basedon two different flow rates from the extracorporeal circuit 100 (and thecorresponding measurements), it is believed that three, four or moreblood flow rates can be established, and the measurements used tofurther calculate the cardiac output, CO, by merely employing additionaliterations of these equations. Thus, in certain configurations there isat least one change in the flow rate from the extracorporeal circuit100, although there can be two, three or more flow rate changes (andcorresponding measured parameters).

In application, the CO of the patient on extracorporeal bloodoxygenation, such as VA-ECMO can be obtained in the followingconfigurations.

In one configuration, the patient, and particularly the circulationsystem 20, is operably connected to the extracorporeal circuit 100,wherein the access line 110, which can include the access cannula asknown in the art, withdraws blood from the patient, and particularly avenous portion of the circulation system 20 and in one configurationfrom the vena cava or the right atria.

The withdrawn blood is passed through the access line 110 through thepump 130 and to the oxygenator 120. The blood is oxygenated in theoxygenator 120 and then pumped through the return line 140 forintroduction to the patient, and particularly the arterial portion ofthe circulation system 20 and more particularly into the aorta orfemoral artery.

To calculate the CO, the amount of oxygenated blood introduced into thecirculation system 20 is measured, such as by reading the setting of thepump 130. However, it is understood alternatively mechanisms can be usedto measure the flow of oxygenated blood, such as by not limited to flowmeters in the extracorporeal circuit 100, dilution measurements orultrasonic measurements as known in the art.

The arterial oxygen saturation, SaO₂, is measured such as by pulseoximetry with the oximeter 60 or arterial blood gas analysis. As seen inFIG. 1 , the pulse oximeter 60 is connected to the patient to measurearterial oxygen saturation, SaO₂.

The venous oxygen saturation, SvO₂, is measured at the inlet of theoxygenator 120 in the extracorporeal circuit 100. It is understood thismeasurement is not of mixed venous oxygenation saturation, and not theblood coming from the lungs, but is rather a surrogate. However, in viewof the invasive nature and potential complications inherent in drawingblood from the pulmonary artery or after the lungs, the measurement ofoxygen saturation from the blood drawn from the inferior vena cava orright atria is used.

It is understood, the method for calculating CO is not limited to themanner of measurement of the parameter upon which the CO is measured.

Then assuming no or negligible lung function and the right atria venoussaturation is close to (or approximates) the mixed venous saturation,then CO is calculated by: [94]

$CO = Q_{b} \times \frac{\left( {100 - SvO_{2}} \right)}{\left( {SaO_{2} - SvO_{2}} \right)}$

-   SaO₂ = saturation of arterial blood-   SvOz = saturation of venous blood withdrawn from the patient from    the right atrium or from the vena cava.

In an alternative configuration employing select equations from above,the patient is operably connected to the extracorporeal circuit 100 asset forth above. It is further understood that although the presentmethod is set forth with specific manner of obtaining measurements, anyavailable manner of obtaining the identified data can be employed.

In this alternative configuration, the amount of oxygenated bloodintroduced into the patient circulation system 20 is measured (oridentified such as by the setting of the pump 130). The arterial oxygensaturation, SaO₂, is then measured by the oximeter 60, such as set forthabove.

The flow rate of oxygenated blood from the extracorporeal circuit 100and introduced to the circulation system 20 is then changed by an amountsufficient to generate a corresponding change to SaO₂. In oneconfiguration, the amount of change is outside of normal operatingvariances, operating error or drift, produces a change in SaO₂ that isalso outside of normal operating variances, operating error and drift,thereby producing a change the reasonably attributable to theintentionally imparted change in the flow rate and resulting change inparameters. Specifically, in one configuration the amount of change inthe flow rate of oxygenated blood from the extracorporeal circuit 100 issufficient to impart a change in the measured SaO₂ that is greater thanoperating error, drift or variance. In some configurations, the changein flow rate of oxygenated blood from the extracorporeal circuit 100 isat least 10% of the original flow rate, and in further configurations atleast 20% of the original flow rate, an in other configurations at least30% of the original flow rate. It is understood the change in flow rateof oxygenated blood from the extracorporeal circuit 100 can be varieddepending on the particular set of circumstances, without deviating fromthe present system.

The change in the flow rate of oxygenated blood from the extracorporealcircuit 100 to the circulation system 20 can be readily imparted bychanging the operation of the pump 130. Thus, the second flow rate ofoxygenated blood is introduced into the circulation system 20.

After changing the oxygenated blood flow rate of the extracorporealcircuit 100, approximately 1 minute to 2 minutes can elapse beforemeasuring, by the oximeter 60, the arterial oxygen saturation SaO₂, forthe second flow rate. That is, the arterial oxygen saturation, SaO₂, ismeasured, such as set forth above during the second flow rate ofoxygenated blood passing into the circulation system 20.

The different second flow rate of oxygenated blood imposed in theextracorporeal circuit 100 is sufficient to impart a change in at leastthe arterial oxygen saturation, SaO₂ that is outside operatingvariances, operating error or drift, such as set forth above.

Of note, there is no need for a measurement of SvOz or a surrogateparameter in this configuration. The CO can then be calculated throughEquations 6 and 7 and Equations 6A and 7A from the measured first andsecond flow rate of oxygenated blood introduced into the circulationsystem 20, and the corresponding arterial oxygen saturation, SaO₂ foreach flow rate.

If indicator dilution techniques are used, it is understood theindicator is any substance that alters a measurable blood property. Theindicator may alter any measurable parameter of the blood. For example,the indicator may be chemical, optical, electrical, thermal or anycombination thereof. The particular indicator is at least partlydictated by the anticipated operating environment. Available indicatorsinclude saline solutions, increased or decreased temperature as well asdyes and various isotopes. The use of temperature differentials may beaccomplished by locally creating a heat source (such as a heater in theoxygenator 120) or a heat sink in the surrounding flow. The creation ofa local temperature gradient offers the benefit of being able to employa dilution indicator without introducing any additional volume into theblood flow. That is, a temperature differential may be created withoutan accompanying introduction of a volume of indicator. Alternatively, avolume of heated or cooled blood may be introduced at the indicatorintroduction port 114 as the indicator. It is also contemplated, that acomponent of the extracorporeal circuit 100 can be controlled to createor induce an indicator within the flow in the extracorporeal circuit.For example, a filtration or treatment rate or heater (chiller) can besufficiently changed to create an effective indicator in theextracorporeal circuit 100 which then travels through thecardiopulmonary system 30.

In a further configuration, a change is a gas exchange between the bloodpassing the extracorporeal blood oxygenation circuit 100 and theoxygenator 120 is imparted over a constant flow rate in theextracorporeal blood oxygenation circuit and a mass balance is appliedto calculate the cardiac output. In a specific configuration, a carbondioxide balance is applied across a change in carbon dioxide in theblood rather than a change of a blood parameter corresponding to achange in the flow rate Q_(b) in the extracorporeal circuit 100.

The purpose of the present system is to provide a simple noninvasivetechnology to measure CO in VA extracorporeal blood oxygenation, such asin a VA ECMO setting. To apply the present technique to measure cardiacoutput CO during VA extracorporeal blood oxygenation, including ECMO,the following terms are employed.

S₁CO₂ - carbon dioxide content leaving lungs coming to the aorta and canbe measured/estimated by capnography of expired air.

S_(a)CO₂ - arterial carbon dioxide content, (which as set forth belowcan be measured by arterial blood sample (arterial blood gas analysis)or estimated via the surrogate, including but not limited toarterialized capillary blood gas analysis; or partial pressure oftranscutaneous carbon dioxide.

S_(ecmo)CO₂ - carbon dioxide content in the blood delivered to thepatient after passing the oxygenator 120, which as set forth herein canbe directly measured from the blood passing to the patient or determinedor calculated via a surrogate like carbon dioxide partial pressuremeasured by the sensors in the outflow of sweep gas air from theoxygenator.

Q_(b) - extracorporeal flow rate, (which as set forth herein can bemeasured by a flow rate of the pump 130 in the extracorporeal circuit100 or readily measured with commercially available flow meters).

CO - Cardiac Output

For purposes of this analysis, it is assumed that the carbon dioxidecontent in the blood, (SCO₂) leaving the oxygenator 120 through theoutlet 210 (S_(ecmo)CO₂) is not materially affected by Q_(b), but ratherpredominantly determined by the sweep gas flow rate in the oxygenator120.

The value of carbon dioxide content in the blood, S_(ecmo)CO₂, can bemeasured by direct blood sampling (arterial blood gas analysis) orestimated via a surrogate or by a sensor of carbon dioxide partialpressure in the outflow air (210) from the oxygenator 120. Any of thecommercially available sensors for measuring the actual carbon dioxidepartial pressure, or surrogate value like carbon dioxide partialpressure, can be used for this measurement.

The surrogate is a value that is related to SCO₂ content which includesbut is not limited to: the partial pressure of CO₂ in the gas, thepartial pressure of CO₂ dissolved in solution, the bicarbonateconcentration of blood, and carbaminohemoglobin concentration. Ingeneral, it is assumed that use of a surrogate rather than the truecontent may be less accurate. It is understood that measuring asurrogate parameter or using a surrogate parameter is encompassed withinmeasuring the named parameter.

Balance Equation

A mass balance equation for CO₂ content in blood can be written for VAECMO as follows:

Q_(b) × S_(ecmo)CO₂ + CO × S_(l)CO₂ = (CO + Q_(b)) × S_(a)CO₂

Where S_(ecmo)CO₂ is the CO₂ (carbon dioxide) content in blood flowingout of the ECMO extracorporeal circuit 100; S₁CO₂ is the CO₂ the inblood leaving the lungs and S_(a)CO₂ is the CO₂ in the arterial blood.

Solving Eq. 9 for CO:

Q_(b) × S_(ecmo)CO₂ + CO × S_(l)CO₂ = CO × S_(a)CO₂ + Q_(b) × S_(a)CO₂

CO × (S_(a)CO₂ − S_(l)CO₂) = Q_(b) × (S_(ecmo)CO₂ − S_(a)CO₂)

$CO = Q_{b} \times \frac{\left( {S_{ecmo}CO_{2} - S_{a}CO_{2}} \right)}{\left( {S_{a}CO_{2} - S_{l}CO_{2}} \right)}$

Currently, during VA ECMO treatment, Q_(b) and S_(ecmo)CO₂ and S_(a)CO₂can be measured or estimated, while S₁CO₂ is difficult to measureaccurately from the expired air. Thus, depending on the confidence inthe S₁CO₂ value, there is one unknown CO in Equation 12, the equationcan still be used for CO assessment based on the present terms, but isless accurate.

Two Balance Equations

To increase the accuracy of the CO measurement with the purpose of theelimination of the potentially unreliable or unknown value of S₁CO₂, andlung influence, the flow rate of the sweep gas through the oxygenator120 can be changed, thus producing a different value of S_(ecmo)CO₂which will change the arterial content of carbon dioxide, S_(a)CO₂.

An increase in the flow rate of the sweep gas (such as via the sweep gasflow rate of the oxygenator 120 and through the outlet 210) willdecrease S_(ecmo)CO₂, and a decrease of the sweep gas flow rateincreases S_(ecmo)CO₂.

Thus, two equations can be produced analogous to Eq. 12 for twodifferent sweep gas flow rates. In the two equation system (one equationfor each sweep gas flow rate), index (1) and index (2) represent thefirst and second sweep gas flow rate, respectively. Upon the assumptionthat the changes in the S₁CO₂ and CO are negligible between the twodifferent sweep gas flow rates, then:

$CO = Q_{b} \times \frac{\left( {S_{ecmo}CO_{2{(1)}} - S_{a}CO_{2{(1)}}} \right)}{\left( {S_{a}CO_{2{(1)}} - S_{l}CO_{2{(1)}}} \right)}$

$CO = Q_{b} \times \frac{\left( {S_{ecmo}CO_{2{(2)}} - S_{a}CO_{2{(2)}}} \right)}{\left( {S_{a}CO_{2{(2)}} - S_{l}CO_{2{(2)}}} \right)}$

Considering if S₁CO₂₍₁₎ = S₁CO₂(₂), then the system of Equations 13 and14 has two unknowns CO and S₁CO₂₍₁₎ = S₁CO₂₍₂₎, and thus can be solvedfor CO:

$CO = Q_{b} \times \left\lbrack {\frac{\left( {S_{ecmo}CO_{2{(1)}} - S_{ecmo}CO_{2{(2)}}} \right)}{\left( {S_{a}CO_{2{(1)}} - S_{a}CO_{2{(2)}}} \right)} - 1} \right\rbrack$

From Equation 15, it can be seen that cardiac output, CO, can bemeasured from a known or measured single extracorporeal flow rate Q_(b)in conjunction with a change in the sweep gas flow rate that provides acorresponding measured change in the (i) arterial carbon dioxidecontent, S_(a)CO₂, which can be measured by arterial blood sample(arterial blood gas analysis) or estimated via a surrogate usingarterialized capillary blood gas analysis, partial pressure oftranscutaneous carbon dioxide or other methods; and (ii) the carbondioxide content in the blood delivered to the patient after passing theoxygenator 120, S_(ecmo)CO₂, (which can be calculated or derived or fromblood sample in blood delivered to patient from the ECMO extracorporealcircuit 100 or estimated via a surrogate like for example, carbondioxide partial pressure or from measurements of sensors in the outflowof sweep gas air from the oxygenator 120 for each flow rate).

In one configuration, the change in the measured carbon dioxide contentsof Eq. 15 is greater than a nominal operating drift or variance.Typically, this magnitude of change results from a magnitude of changein the flow rate of the sweep gas in the oxygenator 120 that is greaterthan normal drift or variance during operation of the oxygenator.

If the decrease of S₁CO₂₍₁₎ is a portion or fraction of the decrease ofthe arterial carbon dioxide content, ΔSaCO₂, (Eq. 13), then the valueS₁CO₂₍₂₎ = S₁CO₂₍₁₎ - K*Δ SaCO₂: where K is for example 0.5 (but couldbe 0.1, 0.2 or 0.7 (or whatever the appropriate factor)), then inEquations 13 and 14 the value S₁CO₂₍₂₎ will be substituted and again, asystem of two equations with two unknowns (CO and S₁CO₂) or (CO₁ andS₁CO₂₍₁₎) is provided, wherein the equations can be solved to determineCO (CO₁).

Further, while the change in the sweep gas has been set forth asproviding the change in carbon dioxide removal, it is understood thatany parameter control that imparts a corresponding change of carbondioxide or another gas or another blood property can be used to measureCO in analogous manner (in place of a specific change in the sweep gas).

Thus, in one configuration, the system includes the controller 160operably connected to a carbon dioxide sensor 220 in the outflow ofsweep gas from the oxygenator 120 from which S_(ecmo)CO₂, is measured(or calculated). However, it is understood S_(ecmo)CO₂ can also bemeasured by blood sample from the arterial line. The controller 160 isalso connected to a sensor or surrogate (such as an exhaled blood gasanalysis or known capnometry) for determining the carbon dioxide contentS₁CO₂.

The controller 160 is programmed with or has access to a memory withlookup tables for converting a surrogate measurement to the respectivecarbon dioxide content as set forth above. In addition, the controller160 is also connected to the pump 130, or a flow meter (not shown) forobtaining the flow rate through the extracorporeal circuit 100. Thecontroller 160 is programmed with the present equations, or equivalents,for calculation of the cardiac output CO.

For purposes of description, the term calculate (or calculating) meansdetermine the amount or number of something mathematically usingmathematics, a mathematical processes or equations, as well as evaluateor estimate the nature, amount or quantity. Calculate or calculatingmeans to discover or identify a number or an amount.

For purposes of description, the term measure (or measuring) means howmuch there is of the relative parameter, including ascertain the size,amount, or degree of (something) such as by using an instrument ordevice marked in standard units or by comparing it with an object ofknown size, wherein the measuring may apply to a surrogate value orsurrogate parameter. For example, for measuring the oxygenated bloodflow rate introduced into the patient circulation system 20, the settingof the pump 130 can be used, a separate flow meter can be used, dilutionmeasurement can be used. It is further contemplated that measuring caninclude a calculating step or steps.

As used herein, the term surrogate is a parameter which is used as ametric for one or more other parameters. Therefore, for purposes ofdescription, when a specific parameter is recited as measured, it isunderstood that such measurement includes a representative of theparameter or a surrogate parameter that is measured, without deviatingfrom the present system. Thus, it is understood that measuring a bloodflow, recirculation or oxygen saturation encompasses measuring therelevant representative parameter as well as measuring a surrogateparameter. For example, it is understood the oxygen content (which mayinclude contribution from other portions of the blood such as theplasma) can be measured in place of arterial oxygen saturation. Althoughthe present analysis is set forth in terms of oxygen saturation, it isintended that oxygen content can be employed and that the recited oxygensaturation encompasses oxygen saturation as well as oxygen content.Thus, it is understood that measuring a blood flow rate, and/or oxygensaturation includes measuring the relevant parameter or measuring asurrogate parameter.

Although the present method and equations are set forth in terms ofoxygen saturation, it is understood that other parameters and/or gasesof the blood can be used in place of the blood oxygen saturation. Thatis, as soon as blood is pumped by the pump 130 in the extracorporealcircuit 100, there will be different physical/chemical property of theblood than the blood flowing in the veins. For example, if the blood iscooled (or heated) in the oxygenator 120, while the blood temperateflowing in the body is at body temperature, then upon measuring thetemperature in the artery, the recorded temperature will be a mixtureand the analogous concept of heat balance can be applied. As usedherein, the term surrogate is a parameter which is used as a metric forone or more other parameters. Therefore, for purposes of description,when a specific parameter is recited as measured, it is understood thatsuch measurement includes a representative of the parameter or asurrogate parameter that is measured, without deviating from the presentsystem. Thus, it is understood that measuring a blood flow,recirculation or oxygen saturation encompasses measuring the relevantrepresentative parameter as well as measuring a surrogate parameter.

It is further contemplated that if the patient were also on aventilator, a rate of respiration could be changed (decreased or eventemporarily halted) to impart a change in a blood parameter to bemeasured.

Thus, in one configuration the present system includes providing atleast a first and a different second flow rate from the extracorporealcircuit 100 wherein a blood parameter is measured on the arterial sideof the patient circulation system during or corresponding to the firstflow rate and the second flow rate. As set forth above in the equations,these values can then be used to calculate cardiac output.

This disclosure has been described in detail with particular referenceto an embodiment, but it will be understood that variations andmodifications can be effected within the spirit and scope of thedisclosure. The presently disclosed embodiments are therefore consideredin all respects to be illustrative and not restrictive. The scope of theinvention is indicated by the appended claims, and all changes that comewithin the meaning and range of equivalents thereof are intended to beembraced therein.

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 18. A method for calculating cardiacoutput of a patient undergoing veno-arterial extracorporeal bloodoxygenation, the method comprising: (a) calculating a cardiac output ofthe patient corresponding to (i) a first blood flow rate from aveno-arterial extracorporeal blood oxygenation circuit into an arterialportion of a patient circulation system, the veno-arterialextracorporeal blood oxygenation circuit including a blood oxygenator,(ii) an arterial blood oxygen saturation, and (iii) a mixed venous bloodoxygen saturation.
 19. The method of claim 18, wherein the patientcirculation system includes a right atrium and a vena cava, and themixed venous blood oxygen saturation is from blood taken from one of theright atrium and the vena cava.
 20. The method of claim 18, wherein themixed venous blood oxygen saturation is from blood not passing throughthe blood oxygenator in the veno-arterial extracorporeal bloodoxygenation circuit.
 21. The method of claim 18, wherein calculating thecardiac output corresponds to$CO = Q_{b} \times \frac{\left( {100 - SaO_{2}} \right)}{\left( {SaO_{2} - SvO_{2}} \right)},$where CO is the cardiac output, Q_(b) is the first blood flow rate, SaO₂is the arterial blood oxygen saturation in the patient circulationsystem, and SvO₂ is the mixed venous blood oxygen saturation in thepatient circulation system.
 22. The method of claim 18, wherein thepatient circulation system includes lungs and the mixed venous bloodoxygen saturation is equal to the oxygen saturation of blood passingfrom the lungs.
 23. The method of claim 18, wherein the arterial bloodoxygen saturation comprises a surrogate parameter for arterial bloodoxygen saturation.
 24. The method of claim 18, wherein the mixed venousblood oxygen saturation comprises a surrogate parameter for the mixedvenous blood oxygen saturation.
 25. The method of claim 18, wherein thearterial blood oxygen saturation, and the mixed venous blood oxygensaturation are measured during the first blood flow rate.
 26. The methodof claim 18, wherein the first blood flow rate is provided by a pump inthe extracorporeal blood oxygenation circuit.
 27. An apparatus forquantifying a cardiac output of a patient operably connected to anextracorporeal blood oxygenation circuit, the extracorporeal bloodoxygenation circuit having an access line withdrawing blood from apatient circulation system, a blood oxygenator, a pump, and a returnline returning oxygenated blood to an arterial portion of the patientcirculation system, the apparatus comprising: (a) a controllerconfigured to connect to one of the blood oxygenator and the pump, thecontroller configured to calculate the cardiac output of the patientcorresponding to a first blood flow rate from the extracorporeal bloodoxygenation circuit to the arterial portion of the circulation system,an arterial blood oxygen saturation, and a mixed venous blood oxygensaturation.
 28. The apparatus of claim 27, wherein the mixed venousblood oxygen saturation is from blood not passing through the bloodoxygenator in the extracorporeal blood oxygenation circuit.
 29. Theapparatus of claim 27, wherein the patient circulation system includes aright atrium and a vena cava, and the mixed venous blood oxygensaturation is from blood taken from one of the right atrium and the venacava.
 30. The apparatus of claim 27, wherein the arterial blood oxygensaturation comprises a surrogate parameter for arterial blood oxygensaturation.
 31. The apparatus of claim 27, wherein the mixed venousblood oxygen saturation comprises a surrogate parameter for the mixedvenous blood oxygen saturation.
 32. The apparatus of claim 27, whereinthe controller is configured to calculate the cardiac outputcorresponding to$CO = Q_{b} \times \frac{\left( {100 - SaO_{2}} \right)}{\left( {SaO_{2} - SvO_{2}} \right)},$where CO is the cardiac output, Q_(b) is the first blood flow rate, SaO₂is the arterial blood oxygen saturation in the patient circulationsystem, and SvO₂ is the mixed venous blood oxygen saturation in thepatient circulation system.
 33. The apparatus of claim 27, wherein thepatient circulation system includes lungs and the mixed venous bloodoxygen saturation is equal to the oxygen saturation of blood passingfrom the lungs.
 34. The apparatus of claim 27, wherein the arterialblood oxygen saturation, and the mixed venous blood oxygen saturationare measured during the first blood flow rate.
 35. The apparatus ofclaim 27, wherein the first blood flow rate is provided by the pump inthe extracorporeal blood oxygenation circuit.